STAT3 inhibition specifically in human monocytes and macrophages by CD163-targeted corosolic acid-containing liposomes

Andersen, Morten Nørgaard; Etzerodt, Anders; Graversen, Jonas Heilskov; Holthof, Lisa C.; Moestrup, Søren K.; Hokland, Marianne; Møller, Holger Jon

doi:10.1007/s00262-019-02301-3

Cited by 50 publications

(32 citation statements)

References 47 publications

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“…It is found that inhibiting the expression of STAT3 reprograms TAMs into M1 macrophages to inhibit tumor growth (159). Indeed, liposomes are used to carry corosolic acid (CA), a natural compound that inhibits stat3, to target CD163+ macrophages, thereby reprogramming TAMs to the M1 phenotype and promoting the expression of pro-inflammatory factors (160). The activation of the STAT3 signal is related to ERK5.…”

Section: Stat3 and Stat6mentioning

confidence: 99%

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

2020

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Tumor microenvironment (TME) is composed of tumor cells and surrounding non-tumor stromal cells, mainly including tumor associated macrophages (TAMs), endothelial cells, and carcinoma-associated fibroblasts (CAFs). The TAMs are the major components of non-tumor stromal cells, and play an important role in promoting the occurrence and development of tumors. Macrophages originate from bone marrow hematopoietic stem cells and embryonic yolk sacs. There is close crosstalk between TAMs and tumor cells. With the occurrence of tumors, tumor cells secrete various chemokines to recruit monocytes to infiltrate tumor tissues and further promote their M2-type polarization. Importantly, M2-like TAMs can in turn accelerate tumor growth, promote tumor cell invasion and metastasis, and inhibit immune killing to promote tumor progression. Therefore, targeting TAMs in tumor tissues has become one of the principal strategies in current tumor immunotherapy. Current treatment strategies focus on reducing macrophage infiltration in tumor tissues and reprogramming TAMs to M1like to kill tumors. Although these treatments have had some success, their effects are still limited. This paper mainly summarized the recruitment and polarization of macrophages by tumors, the support of TAMs for the growth of tumors, and the research progress of TAMs targeting tumors, to provide new treatment strategies for tumor immunotherapy.

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Section: Stat3 and Stat6mentioning

confidence: 99%

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

2020

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“…There are several therapeutic approaches suggested for the inhibition of tumorigenic action of STATs in macrophages. For example, liposome-encapsulated STAT3 inhibitor can activate reprogramming of CD163+TAMs toward pro-inflammatory phenotypes with increased secretion of IFNγ, IL-12, TNFα, IL-2 in vitro [78]. Another study demonstrated that herbal acidic polysaccharide IAPS-2 inhibits the phosphorylation of STAT3 and enhances STAT1 phosphorylation in TAMs from S180 tumor tissues (a syngeneic sarcoma) promoting macrophage polarization toward the M1-like phenotype [79].…”

Section: Stat Familymentioning

confidence: 99%

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Larionova

Kazakova

Patysheva

et al. 2020

Cancers

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Macrophages are key innate immune cells in the tumor microenvironment (TME) that regulate primary tumor growth, vascularization, metastatic spread and tumor response to various types of therapies. The present review highlights the mechanisms of macrophage programming in tumor microenvironments that act on the transcriptional, epigenetic and metabolic levels. We summarize the latest knowledge on the types of transcriptional factors and epigenetic enzymes that control the direction of macrophage functional polarization and their pro- and anti-tumor activities. We also focus on the major types of metabolic programs of macrophages (glycolysis and fatty acid oxidation), and their interaction with cancer cells and complex TME. We have discussed how the regulation of macrophage polarization on the transcriptional, epigenetic and metabolic levels can be used for the efficient therapeutic manipulation of macrophage functions in cancer.

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“…Different studies have shown that genetic or epigenetic reprogramming of M2-like TAMs into M1-like TAMs in the TME has promising effects. Specific STAT3 inhibition in human monocytes and macrophages by CD163-targeted corosolic acid-containing liposomes promotes M1-like TAMs reprogramming, inhibits STAT3-regulated IL-10 expression and increases pro-inflammatory TNFα levels (84). Paclitaxel alters the signature of TAMs in the TME from a M2-like pro-tumor profile (CD206, RELMα, MMP9 and ARG1) to a M1-like antitumor profile (IL12, iNOS and IL6), inducing tumor regression by reprogramming in a TLR4-dependent manner in mouse models of breast and melanoma tumors (85) ( Table III).…”

Section: Potential Strategies For Tams-targeted Cancer Immunotherapymentioning

confidence: 99%

Targeting tumor‑associated macrophages in the tumor microenvironment (Review)

et al. 2020

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Tumor-associated macrophages (TAMs) are the most abundant population type of tumor-infiltrating immune cells found in the tumor microenvironment (TME), and are evolutionarily associated with microvessel density in tumor tissues. TAMs can be broadly divided into M1-like and M2-like TAMs, which demonstrate antitumor and pro-tumor activity in the TME, respectively. Studies have indicated that: i) The predominate presence of M2-like TAMs in the TME can result in tumor immunosuppression and chemoresistance; ii) the ratio of M1-like to M2-like TAMs in the TME is positively correlated with better long-term prognosis of patients with cancer; iii) epigenetic silencing, preventing the secretion of M1-like TAM-associated molecules, is an important immune evasion mechanism during tumor progression; and iv) the transformation from M2-like to M1-like TAMs following exposure to specific conditions can result in tumor regression. The present study discusses the molecular events underlying the recruitment of macrophages and their polarization into M1-like or M2-like TAMs, and their differential roles in angiogenesis, angiostasis, invasion, metastasis and immune activity in the TME. This insight may inform the improved design of TAM-targeted cancer immunotherapy. Some of these therapeutic strategies show promising effects; however, challenges remain.

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STAT3 inhibition specifically in human monocytes and macrophages by CD163-targeted corosolic acid-containing liposomes

Cited by 50 publications

References 47 publications

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

The Crosstalk Between Tumor-Associated Macrophages (TAMs) and Tumor Cells and the Corresponding Targeted Therapy

Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages

Targeting tumor‑associated macrophages in the tumor microenvironment (Review)

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